Credit: NIAID

Oxford vaccine trial on hold – Expert Reaction

An investigation is underway after a participant in the Oxford/AstraZeneca coronavirus vaccine trial fell seriously ill.

AstraZeneca is investigating whether the reaction was directly caused by the vaccine or was coincidental. Unconfirmed reports say it is a case of transverse myelitis, an inflammatory condition that affects the spinal cord.

The SMC asked experts to comment.

Associate Professor Helen Petousis-Harris, Vaccinologist, University of Auckland, comments:

These comments are excerpted from this blog post on SciBlogs.

“With over 200 COVID-19 vaccines now under development we are going to start seeing participants in the clinical trials have heath events. These events may or may not be completely unrelated to the vaccine under study. When you have what will ultimately be hundreds of thousands of people under observation in clinical trials, some will get sick, especially when you start recruiting older people into these studies. When this happens sometimes the trial will need to be halted while the event is investigated, and a lot of questions answered.”

What does the halting of a trial mean?

“As the COVID-19 vaccine trials progress we are going to see periodic haltings of these trials. This is actually the second time the Oxford/AstraZeneca vaccine trials have paused. One reason for halting a trial is because a participant has had an adverse medical event. We must accept the possibility that one, or some, of these new vaccines may have safety problems and fail to progress further. We must also accept that if the event has been determined not caused by the vaccine the trial may resume. This is normal practice.”

What does this mean for COVID-19 vaccines?

“This event does not affect other trials, particularly those using different vaccine platforms. It also demonstrates that safety is being taken very seriously. We need to be patient and let the trials run their course.”

The UK Science Media Centre has also gathered the following comments:

Professor Ian Jones, Professor of Virology, University of Reading, comments:

“An inevitable consequence of testing a vaccine on large numbers of people is that some will naturally fall ill of other causes during the trial. A similar incident some ten years ago during the roll out of the HPV vaccine resulted in the immediate quarantine of a batch of the vaccine, although the overall programme was not suspended. We must wait and see what the investigation in this case shows but at the moment, I think unfortunate more than sinister would be the best description of the halt.”

No conflict of interest.

Professor Saad Shakir, Director of the Drug Safety Research Unit (DSRU) in Southampton, comments:

“This is a standard procedure in clinical research in response to detecting a serious event.

“It gives the study team and the independent advisory board time to evaluate the details of the event and to decide the causal association between the vaccine and the event. The key objectives are to assess the risks for those who have already been vaccinated and, as a precaution, to protect people who are due to be vaccinated.

“There were no serious adverse reactions in the phase 1/2 study of this vaccine, which was published in The Lancet in July. The study included 1,077 vaccinees who were observed for eight weeks. This appears to be the first serious event with this vaccine.

“There are unconfirmed reports about the specific nature of the condition. But we need to hear from the study team themselves, once they have fully investigated the matter, before we can assess the impact of this event on the development of the Oxford vaccine.”

No conflict of interest.

Dr Ohid Yaqub, Senior Lecturer at the SPRU (Science Policy Research Unit), University of Sussex, comments:

“A suspension such as this is not unusual for phase 3 trials, which have tens of thousands of participants.

“Suspending the trial gives time to investigate whether the incident is related to the vaccine or is happening by coincidence. If the data and safety monitoring board decides it’s the latter, the trial will resume. Other trials will also investigate their data too.

“In some senses, it is good that such a routine event is being publicised because it helps to build trust as it provides an opportunity for people to see the procedures at work. But there is a balance to be struck with respect to how much detail is released as a running commentary about the trial so far, because it may bias the results. Those details will be released at the end of the trial.”

No conflict of interest.

Dr Charlie Weller, Head of Vaccines Programme at Wellcome, comments:

“Safety is the most important consideration when developing any vaccine, and it is right for the trial to be paused while an investigation takes place. This is often a normal part of the process in vaccine trials, which involve tens of thousands of people. It’s critical to quickly understand whether the illness has any relationship to the vaccine or the placebo and to share data openly, as Oxford University and AstraZeneca have done.

“Vaccines are among the most rigorously tested and monitored products we have in society, and the COVID-19 vaccines should be no different. We welcome the news that nine vaccine developers have pledged to uphold scientific and ethical standards for these vaccines and prioritise safety.

“Today’s news reminds us of the importance of funding and developing a wide range of vaccine candidates, alongside treatments and testing. We don’t yet know which will be successful, but ensuring all advances are fairly available globally is our only exit from this pandemic.”

No conflict of interest.

Dr James Gill, Honorary Clinical Lecturer, Warwick Medical School, and Locum GP, comments:

“During the development of any drug, people will develop side effects – hence we know ibuprofen can cause heart burn. People will also fall ill during the natural course of their lives whilst they have taken the vaccine – we know that the ‘flu vaccine doesn’t cause ‘flu but some people can be unlucky and catch a bug around the time they are inoculated.

“It is crucial that we remember correlation – i.e. things happening at the same time – does not mean causation – i.e. the two things happening can be coincidental.

“The fact that the AstraZenca and Oxford developed vaccine trial has been temporarily paused should be paradoxically considered a good thing

“Whilst it has been reported that one trial volunteer has become ill, this may be due to an issue related to the vaccine. It also may not. That the trial has announced this, and has placed a pause on the testing to allow an independent panel to look into the event, should be championed as good science and great transparency for the public who are waiting for news on a COVID-19 vaccine.

“Personally, I would be suspicious of a vaccine for a novel virus which was developed without any hiccoughs or pauses. Science on TV is great, and usually gets completed in the course of an episode. In a real lab, chemistry, patients and biology don’t often follow a nice simple course, which is why from the start scientists have said that this COVID vaccine development will take considerable time to get right and safe.”